This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Globoid cell leukodystrophy, or Krabbe's disease, is a severe disorder of the central and peripheral nervous system caused by the absence of galactocerebrosidase (GALC) activity. We have previously determined that rhesus macaques affected with Krabbe's disease demonstrated marked increases in the levels of expression of iNOS, TNF-alpha, and IL-1 in the affected white matter, colocalizing with globoid cells, activated microglia, and astrocytes. Cytokine mRNA levels revealed markedly increased gene expression of CCL2 in the brain of affected macaques. CCL2-expressing cells were detected throughout the affected white matter, colocalizing with GFAP cells and astrocytes. We are presently performing as complete analysis of cytokine alterations using a Bioplex analysis at various stages of disease progression. Krabbe brain white matter samples are being directly compared to age and sex matched control brain samples form unaffected animals. In addition, we have begun studies to investigate the role of the inflammatory processes on disease progression. It is hoped that this analysis will provide insight into the role that the inflammatory process plays in the disease progression and to identify potential targets for therapeutic intervention.